ArticleAntimicrobial agents and chemotherapy2011
Regulation of efflux pump expression and drug resistance by the transcription factors Mrr1, Upc2, and Cap1 in Candida albicans.
Article in Antimicrobial agents and chemotherapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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83 citing papers in PubMed, 133 citations in OpenAlex.
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- Molecular frontiers of fungal autophagy: from molecular mechanisms to potential targets for antifungal drug discovery.World journal of microbiology & biotechnology · 2026Review
- Azole Resistance in Candida parapsilosis From Patients With Burns in Mexico: A Genomic and Phylogenetic Analysis.Mycoses · 2026Article
- Recurrent mutations in the stress regulator Cap1 reveal a trade-off between azole resistance and oxidative stress response in Candida albicans.PLoS biology · 2026Article
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- Transcription factor Hap2p regulates antioxidant stress responses to maintain miconazole resistance inMycology · 2025Article
- Adaptation of Candida albicans to specific host environments by gain-of-function mutations in transcription factors.PLoS pathogens · 2024Review
- Single-cell detection of copy number changes reveals dynamic mechanisms of adaptation to antifungals in Candida albicans.Nature microbiology · 2024Article
- Investigating role of positively selected genes and mutation sites of ERG11 in drug resistance of Candida albicans.Archives of microbiology · 2024Article
- Probing gene function inmSphere · 2024Article
- A gain-of-function mutation in zinc cluster transcription factor Rob1 drives Candida albicans adaptive growth in the cystic fibrosis lung environment.PLoS pathogens · 2024Article
- Upc2-mediated mechanisms of azole resistance inMicrobiology spectrum · 2024Article
- Insights into the structure, function, and impact ofCurrent medical mycology · 2024Review
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- The Microevolution of Antifungal Drug Resistance in Pathogenic Fungi.Microorganisms · 2023Review
- Broad susceptibility ofmBio · 2023Article
- Involvement of AoMdr1 in the Regulation of the Fluconazole Resistance, Mycelial Fusion, Conidiation, and Trap Formation ofMicroorganisms · 2023Article
- Article
23 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
Constitutive overexpression of the Mdr1 efflux pump is an important mechanism of acquired drug resistance in the yeast Candida albicans. The zinc cluster transcription factor Mrr1 is a central regulator of MDR1 expression, but other transcription factors have also been implicated in MDR1 regulation. To better understand how MDR1-mediated drug resistance is achieved in this fungal pathogen, we studied the interdependence of Mrr1 and two other MDR1 regulators, Upc2 and Cap1, in the control of MDR1 expression. A mutated, constitutively active Mrr1 could upregulate MDR1 and confer drug resistance in the absence of Upc2 or Cap1. On the other hand, Upc2 containing a gain-of-function mutation only slightly activated the MDR1 promoter, and this activation depended on the presence of a functional MRR1 gene. In contrast, a C-terminally truncated, activated form of Cap1 could upregulate MDR1 in a partially Mrr1-independent fashion. The induction of MDR1 expression by toxic chemicals occurred independently of Upc2 but required the presence of Mrr1 and also partially depended on Cap1. Transcriptional profiling and in vivo DNA binding studies showed that a constitutively active Mrr1 binds to and upregulates most of its direct target genes in the presence or absence of Cap1. Therefore, Mrr1 and Cap1 cooperate in the environmental induction of MDR1 expression in wild-type C. albicans, but gain-of-function mutations in either of the two transcription factors can independently mediate efflux pump overexpression and drug resistance.
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